Science

Tissue Factor

Tissue Factor Overexpression Involved in Many Diseases
Tissue factor (TF) is a naturally-occurring protein in humans that plays an important role in the coagulation cascade, a complex set of processes that produce a blood clot in response to an injury. When TF is overexpressed, however, it causes inflammation and angiogenesis (abnormal growth of blood vessels), which often produce undesirable consequences for patients. TF overexpression plays a pivotal role in multiple diseases, including wet age-related macular degeneration (AMD) and cancer.

Because of TF’s critical role in the underlying pathology, several biopharma companies have attempted to develop therapeutics that target and inhibit TF overexpression. Although TF is a well understood target for drug development, TF-targeted therapies have proven challenging to develop because of safety concerns.

Innovative Approach to Targeting TFIconic Therapeutics, using insight, ingenuity and an in-depth understanding of TF biology, has overcome these challenges and made TF a druggable target. Taking an innovative approach to developing agents against TF, we engineered a synthetic protein that is able to bind to TF without appreciably affecting the coagulation cascade.

This molecule, called ICON-1, is an immunoconjugate fusion protein. It combines a targeting domain with a modified Factor VII, which binds to TF, with an effector domain that can engage Fc bearing cells. ICON-1 is in development for the treatment of patients with wet age-related macular degeneration (AMD), which is characterized by TF overexpression.

Based on our in-depth understanding of TF, our expertise in engineering proteins to bind to this target, and our previous experience developing and manufacturing ICON-1, we are developing multiple anti-TF therapeutics based on different protein scaffolds. We are advancing two pre-clinical programs targeting TF for both wet AMD and solid tumors.